Composition for enhancing physical performance

ABSTRACT

This invention relates to a composition that contains quercetin, vitamin B1, vitamin B2, vitamin B3, vitamin B6, vitamin B12, vitamin C, caffeine, epigallocatechin gallate, epicatechin, epicatechin gallate, and epigallocatechin.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.11/675,576, filed Feb. 15, 2007, which is a continuation of U.S.application Ser. No. 10/692,178, filed Oct. 23, 2003, which is acontinuation-in-part of U.S. application Ser. No. 10/302,544, filed Nov.22, 2002, now U.S. Pat. No. 6,821,536, issued Nov. 23, 2004. U.S.application Ser. No. 10/692,178 claims the benefit of U.S. ProvisionalApplication No. 60/420,986, filed Oct. 23, 2002. The contents of all theforegoing applications are incorporated herein by reference in theirentireties.

BACKGROUND

Achieving peak physical performance has long been a goal for athleticcompetition and self-improvement. Means for improving physicalperformance includes prolonged systematic exercise, proper diet, and useof pharmaceuticals such as anabolic steroids. Anabolic steroids, whichare testosterone derivatives, promote tissue growth, increase musclemass, increase blood volume and hemoglobin level, and improve overallstrength. Nonetheless, the use of anabolic steroids often results inserious complications, such as decreased blood high-density lipoproteinlevels, disorders of the reproductive system, and disorders of the liverincluding carcinoma and peliosis hepatis. These complications furtherlead to virilization in females, interrupted growth in children, anddefects in fetuses. The use of anabolic steroid can also causepsychological disorders such as unpredictable mood changes andaggression. Thus, there is a need for a safe drug or dietary supplementfor enhancing physical performance.

SUMMARY

This invention relates to a composition that contains quercetin and anumber of other natural products. The composition can be used inenhancing physical performance, i.e., improving an ability to perform anexercise, such as speed, strength, power, endurance, flexibility,agility, balance, focus coordination, reaction time, and fatiguerecovery.

One aspect of this invention features a composition that containsquercetin and one or both of vitamin B3 and C. In one embodiment, thecomposition further contains at least one of the following ingredients:vitamin B1, vitamin B2, vitamin B6, and vitamin B12. In anotherembodiment, it further contains at least one of caffeine,epigallocatechin gallate, epicatechin, epicatechin gallate,epigallocatechin, and polypheron E. This composition may also containother ingredients, such as vitamin E, CoQ-10, soy isoflavones, taurine,sugar beet pectin fiber, and a ginko biloba extract. Further, thecomposition can be sweetened, if necessary, by adding a sweetener, e.g.,sorbitol, maltitol, cane sugar, high fructose corn syrup, and the like.The composition can also contain amino acids, minerals, a flavorenhancer, or a coloring agent. It is known that the leaves of green teacontain epigallocatechin gallate, epicatechin, epicatechin gallate,epigallocatechin, and polypheron E. Thus, these five ingredients can beconveniently provided as a green tea extract.

The composition of the invention can be in dry form (e.g., power ortablet) or in aqueous form (e.g., beverage or syrup). It can be adietary supplement or a pharmaceutical formulation. It can also be adrink or a food product. Examples include tea (e.g., a tea drink and thecontents of a tea bag), soft drinks, juice (e.g., a fruit extract and ajuice drink), milk, coffee, jelly, ice cream, yogurt, cookies, cereals,chocolates, and snack bars. The composition, in any of the formsdescribed above, can be used to enhance physical performance. Alsowithin the scope of this invention is a composition of the invention asan active agent, as well as use of the composition for the manufactureof a medicament, for enhancing physical performance.

The invention also features a method for enhancing physical performance.The method includes administering to a subject in need thereof aneffective amount of the above-described composition. By properadministrating the composition as detailed below, physical performancecan be enhanced without the deleterious side effects of pharmaceuticalperformance enhancers, such as anabolic steroids.

The details of one or more embodiments of the invention are set forth inthe accompanying description below. Other features, objects, andadvantages of the invention will be apparent from the description andfrom the claims.

DETAILED DESCRIPTION

This invention is based, at least in part, on the unexpected discoverythat quercetin, an antioxidant, and a number of other natural productsexhibit synergistic health benefits, including enhancing physicalperformance in a subject.

For example, within the scope of this invention is aquercetin-containing composition that includes vitamin B3 or vitamin C,or both. It further contains one or more of vitamin B1, vitamin B2,vitamin B6, and vitamin B12. The composition can also contain one ormore of caffeine, epigallocatechin gallate, epicatechin, epicatechingallate, epigallocatechin, and polypheron E. A green tea extract can beconveniently used to provide epigallocatechin gallate, epicatechin,epicatechin gallate, epigallocatechin, and polypheron E.

Exemplary quantities of the ingredients of this composition are: 0.1-50mg of vitamin B1, 0.1-150 mg of vitamin B2, 0.1-2000 mg of vitamin B3,0.1-200 mg of vitamin B6, 5-150 .mu.g of vitamin B12, 50-2000 mg ofvitamin C, 50-1500 mg of caffeine, 20-2000 mg of quercetin, 10-500 mg ofepigallocatechin gallate, 10-500 mg of epicatechin, 10-500 mg ofepicatechin gallate, 10-500 mg of epigallocatechin, and 10-5-mg ofpolypheron E, which can be dissolved or dispersed in a 1 L aqueoussolution. The quantities of the ingredients can also be those of thesame relative ratio to those listed above. The term “quercetin” refersto both quercetin aglycon and quercetin derivatives, e.g.,quercetin-3-O-glucoside, quercetin-5-O-glucoside,quercetin-7-O-glucoside, quercetin-9-O-glucoside,quercetin-3-O-rutinoside,quercetin-3-O-[.alpha.-rhamnosyl-(1.fwdarw.2)-.alpha.-rhamnosyl-(1.fwdarw-.6)]-.beta.-glucoside,quercetin-3-O-galactoside, quercetin-7-O-galactoside,quercetin-3-O-rhamnoside, and quercetin-7-O-galactoside. Afterdigestion, quercetin derivatives are converted to quercetin aglycon, anactive form absorbed in the body. The quantity of quercetin mentionedabove refers to that of quercetin aglycon or the quercetin moiety of aquercetin derivative. As an example, a composition for daily used can bea 1 L aqueous solution containing 1000 mg of quercetin, 30 mg of vitaminB1, 85 mg of vitamin B2, 1 g of vitamin B3, 100 mg of vitamin B6, 120.mu.g of vitamin B12, 1200 mg of vitamin C, 1000 IU of vitamin E, 1000mg of caffeine, and a green tea extract containing 120 mg ofepigallocatechin gallate, 140 mg of epicatechin, 360 mg of epicatechingallate, 360 mg of epigallocatechin, and 120 mg of polypheron E.

This composition may also contain one or more other active ingredients,such as vitamin E, CoQ-10, soy isoflavones, taurine, sugar beet pectinfiber, and a ginko biloba extract. Exemplary quantities of theseingredients are: 3-1000 IU of vitamin E, 10-400 mg of CoQ-10, 20-600 mgof soy isoflavones, 10-1000 mg of taurine, 1-15 g of sugar beet pectinfiber, and 50-500 mg of a ginko biloba extract (dry weight). Further,the composition can be sweetened, if necessary, by adding a sweetenersuch as sorbitol, maltitol, hydrogenated glucose syrup and hydrogenatedstarch hydrolyzate, high fructose corn syrup, cane sugar, beet sugar,pectin, and sucralose.

An example of the above-describes composition is a powder. It can beused conveniently to prepare beverages, e.g., tea or juice. The powdercan also be used to prepare paste, jelly, capsules, or tablets. Lactoseand corn starch are commonly used as diluents for capsules and ascarriers for tablets. Lubricating agents, such as magnesium stearate,are typically added to form tablets.

The composition of the invention can also be a dietary supplement or apharmaceutical formulation. As a dietary supplement, additionalnutrients, such as minerals or amino acids may be included. Thecomposition can also be a drink or food product. As used herein, theterms “drink” and “food” broadly refer to any kinds of liquid andsolid/semi-solid materials, respectively, that are used for nourishingan animal, and for sustaining normal or accelerated growth of an animalincluding a human. Examples of the drink product include, but are notlimited to, tea-based beverages, juice, coffee, and milk. Examples ofthe food product include jelly, cookies, cereals, chocolates, snackbars, herbal extracts, dairy products (e.g., ice cream, and yogurt), soybean product (e.g., tofu), and rice products.

The above-described composition, in any of the forms described above,can be used for enhancing physical performance. As shown in the examplesbelow, the composition improves overall strength, balance, fatiguerecovery, intensity of physical exercise, and endurance to the exercise.It can also be used for treating diseases or disorders, such asarthritis, tumor, diabetes, sexual dysfunction, chronic constipation,inflammatory bowel disease; improving concentration or mood; andlowering cholesterol levels of blood pressure. A “tumor” refers tobenign tumor, as well as malignant tumor (e.g., leukemia, colon cancer,kidney cancer, liver cancer, breast cancer, or lung cancer).

The terms “improving”, “treating,” and “lowering” refer to theadministration of an effective amount of a composition of the inventionto a subject, who needs to improve his physical performance or has oneor more of the just-mentioned disorders, or symptom or a predispositionof one of more of the disorders, with the purpose to improve physicalperformance or to cure, alleviate, relieve, remedy, or ameliorate one ormore of the disorders, or the symptoms or the predispositions of one ormore of them. The term “administration” covers oral or parenteraldelivery to a subject a composition of the invention in any suitableform, e.g., food product, beverage, tablet, capsule, suspension, andsolution. The term “parenteral” refers to subcutaneous, intracutaneous,intravenous, intramuscular, intraarticular, intraarterial,intrasynovial, intrasternal, intrathecal, intralesional, andintracranial injection, as well as various infusion techniques. An“effective amount” refers to a dose of the composition that issufficient to provide a physical benefit (e.g., improving endurance) ora therapeutic benefit (e.g., lowering cholesterol levels or bloodpressure). Both in vivo and in vitro studies can be conducted todetermine optimal administration routes and doses.

The specific examples below are to be construed as merely illustrative,and not limitative of the remainder of the disclosure in any waywhatsoever. Without further elaboration, it is believed that one skilledin the art can, based on the description herein, utilize the presentinvention to its fullest extent. All publications cited herein arehereby incorporated by reference in their entirety.

Example 1

Composition A (1000 ml) was prepared by mixing the following ingredientsat room temperature: 1000 ml of orange juice, 1000 mg of quercetin, 30mg of vitamin B1, 85 mg of vitamin B2, 1000 mg of vitamin B3, 100 mg ofvitamin B6, 120 .alpha.g of vitamin B12, 1000 IU of vitamin E, and 1000mg of caffeine. All ingredients were obtained from Spectrum Laboratoryproducts, Inc., Gardena, Calif.; Sigma, St. Louis, Mo.; and Aldrich,Milwaukee, Wis.

Ten male Spregue-Dawley rats, weighing 240-250 g, were obtained fromCharles River Lab (Boston, Mass.). The rats were divided into Groups 1and 2 (5 in each group). The rats in the Group 2 were administered byintragastric feeding with the just-described composition at a daily doseof 8 ml/rat (30 ml/kg body weight) for 48 days. The rats in Group 1 wereadministered with water.

At days 0, 14, 28, and 42 after the administration, blood samples werecollected from the rats by supraorbital bleeding and varioushematological parameters were determine using standard methods. Theresults are summarized in Tables 1 and 2 below.

TABLE 1 Effects of composition A on rat hemotological parameters Effectsof composition A on rat hemotological parameters Reference Day 0 Day 14Day 28 Day 42 Parameter Range Group 1 Group 2 Group 1 Group 2 Group 1Group 2 Group 1 Group 2 WBC  9.4-14.9 17.22 15.04 17.34 16.50 18.7616.90 17.66 14.20 (THSN/UL) RBC 6.2-9.0 6.09 5.94 6.63 6.60 7.43 7.207.99 7.72 (MILL/UL) Hb 13.4-16.4 12.46 12.38 14.24 14.40 15.32 15.0215.86 15.18 (GM/DL) Hematocrit 40.0-49.0 37.80 37.44 42.30 43.26 45.5645.00 47.04 45.86 (%) MCV 52.0-66.0 62.20 63.20 63.80 65.40 61.60 62.6058.80 59.40 (FL) MCH 17.7-19.1 20.46 20.84 21.50 21.82 20.68 20.86 19.8819.72 (PICO GM) MCHC 32.0-33.5 32.96 33.00 33.64 33.26 33.66 33.38 33.7233.14 (%) Platelet  780-1400 956.00 965.00 1084.60 1158.80 1078.401076.60 967.00 962.80 (THSN/UL) BANDS 0.00-0.06 0.00 0.00 0.00 0.00 0.000.00 0.00 0.00 (THSN/UL) Segmented 0.58-6.30 4.44 4.78 3.34 3.59 3.413.33 3.27 3.60 Nestrophiles (THSN/UL) Lymphocyte 3.78-14.9 10.07 7.8412.10 11.02 13.52 11.99 12.78 9.37 (THSN/UL) Monocyte 0.02-1.20 3.432.15 1.67 1.67 1.49 1.30 1.24 1.03 (THSN/UL) Eosinophiles 0.00-0.01 0.540.16 0.11 0.10 0.17 0.13 0.20 0.10 (THSN/UL) Basophiles 0.00-0.00 0.140.11 0.12 0.12 0.17 0.15 0.16 0.09 (THSN/UL) Atipicle 0.00-0.00 0.020.00 0.00 0.00 0.00 0.00 0.00 0.00 Lymphocyte (THSN/UL) Metamyelocytes0.00-0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 (THSN/UL) Myelocytes0.00-0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 (THSN/UL) NRBC/100WBC0-0 0.60 0.40 0.00 0.00 0.00 0.00 0.00 0.00 (/100WBC) Reticulocyte0.1-4.0 1 1 2.62 5.74 3.30 5.90 4.78 6.58 (%) Note: WBC: white bloodcell RBC: red blood cell Hb: hemoglobin MCV: mean corpuscular volumeMCH: hemoglobin amount per red blood cell MCHC: mean cell hemoglobinconcentration BANDS: premature neutrophil NRBC: nucleated red blood cellcount THSN/UL: 1,000/μl MILL/UL: 1,000,000/μl GM/DL: gram/dl FL:femtoliter PICO GM: pictogram

TABLE 2 Effects of composition A on rat reticulocyte level Effects ofcomposition A on rat reticulocyte level Ref Reticulocyte level Range ineach rat Group (%) Day 1# 2# 3# 4# 5# Average SD 1 0.1-4.0 14 2.9 2.9 24.9 4.4 2.62 0.96 2 0.1-4.0 14 5.8 4.9 7.5 5.8 4.7 5.74 2.15 1 0.1-4.028 3.1 2.2 2.2 7.2 6.8 3.30 2.5  2 0.1-4.0 28 4.8 6.5 5.4 5.5 7.3 5.901.3  1 0.1-4.0 42 4.8 9.2 9 5.5 5.4 4.78 2.14 2 0.1-4.0 42 7.5 6.2 6.16.4 6.7 6.58 0.16 Note: SD = Standard Deviation

As shown in Tables 1 and 2, the reticulocyte levels in the ratsadministered with composition B (Group 2) were higher than those in therats administered with water (Group 1). For example, at Day 42, theaverage reticulocyte level in the rats of Group 2 (6.58%) was higherthan that in the rats of Group 1 (4.78%) by 37.7%. On the other hand,other hematological parameters of the rats in the two groups did notdiffer significantly. See Table 1. The results indicate that compositionA increases the reticulocyte level but does not affect otherhematological parameters. Reticulocytes are immature, anucleated redblood cells (RBCs). An increase in the reticulocyte level and no changesin other hematological parameters suggest that composition A improvesthe renewal of RBC.

During the experiment, the body weight of each rat was monitored daily.No statistical difference was found between the two groups.

Example 2

Composition B (1000 ml) was prepared by mixing the following ingredientsat room temperature: 1000 ml of orange juice, 1000 mg of quercetin, 30mg of vitamin B1, 85 mg of vitamin B2, 1000 mg of B3, 100 mg of vitaminB6, 120 .mu.g of vitamin B12, 1000 IU of vitamin E, 1000 mg of caffeine,500 mg of epigallocatechin gallate, 500 mg of epicatechin, 500 mg ofepicateqin gallate, 500 mg of epigallocatechin, and 500 mg of polypheronE.

Ten male Spregue-Dawley rats that weighted 240-250 g were divided intoGroups 1 and 2 (5 in each group). The rats in Group 2 were administeredby intragastric feeding with composition B at an average daily dose of14 ml/kg body weight for 95 days. Those in Group 1 were administeredwith water.

Starting form Day 92 after the administration, each of the rats wastrained on a Rota-Rod treadmill (Model 57750, Stoelting Co., Wood Dale,Ill.) for over 2 hours. At Day 95, after being trained for another 20minutes, each of the rats was put on the treadmill and allowed to walk.The time for which each rat walked on the treadmill before falling offwas recorded and the average time for the rats in Groups 1 and 2determined. The experiments were repeated for three times (“Test A,”“Test B,” and “Test C”). The results are summarize in Table 3 below.

TABLE 3 Effects of composition B Time on Rota-Rod treadmill (min) GroupsTest A Test B Test C Group 1 #1 2.36 13.11 23.33 #2 10.69 16.02 44.21 #319.02 15.46 66.90 #4 2.99 16.67 16.09 #5 1.34 3.41 7.82 Average 7.2812.93 31.67 SE 3.37 2.45 10.68 Group 2 #1 6.54 61.95 80.40 #2 16.1621.54 41.73 #3 6.91 23.83 90.47 #4 24.19 20.42 202.82 #5 32.58 15.3767.44 Average 17.28 28.62 96.57 SE 5.03 8.45 27.79 Note: SE = StandardError

As shown in Table 3, the rats got used to the exercise and walked forlonger time on the treadmill as the experiment went on. In all tests,the rats that had been administered with composition B walked on thetreadmill longer than those that had been not. These results indicatethat composition B enhanced the physical performance of rats. During the95 days of administration, the body weight of each rat was monitoreddaily. No statistical difference was found between Groups 1 and 2. Thisresult suggests the enhanced physical performance of the rats in Group 2was not due to an increase in body mass.

Other Embodiments

All of the features disclosed in this specification may be combined inany combination. Each feature disclosed in this specification may bereplaces by an alternative feature serving the same, equivalent, orsimilar purpose. Thus, unless expressly stated otherwise, each featuredisclosed is only an example of a generic series of equivalent orsimilar features.

From the above description, one skilled in the art can easily ascertainthe essential characteristics of the present invention, and withoutdeparting from the spirit and scope thereof, can make various changesand modifications of the invention to adapt it to various usages andconditions. Thus, other embodiments are also within the scope of thefollowing claims.

1. A composition comprising quercetin, vitamin B1, vitamin B2, vitaminB3, vitamin B6, vitamin B12, vitamin C, and at least one catechin. 2.The composition of claim 1, wherein said catechin is selected from thegroup consisting of epigallocatechin gallate, epicatechin, epicatechingallate, and epigallocatechin.
 3. The composition of claim 2 comprising20-2000 mg quercetin, 0.1-50 mg vitamin B1, 0.1-150 mg vitamin B2,0.1-2000 mg vitamin B3, 0.1-200 mg vitamin B6, 5-150 μg of vitamin B12,50-2000 mg vitamin C, 10-500 mg epigallocatechin gallate, 10-500 mgepicatechin, 10-500 mg epicatechin gallate, and 10-500 mgepigallocatechin, or quantities of the same relative ratios.
 4. Thecomposition of claim 1, further comprising vitamin E.
 5. The compositionof claim 3, further comprising-1000 IU vitamin E or a quantity ofvitamin E in the same relative ratio to other components of saidcomposition.
 6. The composition of claim 1, further comprising CoQ-10,soy isoflavones, taurine, sugar beet pectin fiber, or a ginko bilobaextract.
 7. The composition of claim 6, wherein said compositioncomprises 10-400 mg CoQ-10, 20-600 mg soy isoflavones, 10-1000 mgtaurine, 1-15 g sugar beet pectin fiber, and 50-500 mg ginko bilobaextract, or quantities of the same relative ratios.
 8. The compositionof claim 1, wherein said catechin is present in a green tea extract. 9.The composition of claim 8, wherein said green tea extract comprisespolypheron E.
 10. The composition of claim 1, wherein the compositioncomprises an aqueous solution.
 11. The composition of claim 1, whereinthe composition comprises a drink or food product.
 12. The compositionof claim 11, wherein the drink or food product is selected from tea,soft drinks, juice, milk, coffee, cookies, cereals, chocolates, or snackbars
 13. A method of enhancing recovery in a subject after exercisecomprising administering the composition according to claim 1 to thesubject.
 14. The method of claim 13, wherein the composition isadministered prior to the exercise.
 15. A method of improving endurancein a subject during exercise comprising administering the compositionaccording to claim 1 to the subject.
 16. The method of claim 13, whereinthe composition is administered prior to the exercise.
 17. A method ofreticulocyte levels in a subject comprising administering thecomposition according to claim 1 to the subject.